Abstract
BackgroundMost epidemiological studies on the interplay between iron deficiency and malaria risk classify individuals as iron-deficient or iron-replete based on inflammation-dependent iron markers and adjustment for inflammation by using C-reactive protein (CRP) or α-1-acid glycoprotein (AGP). The validity of this approach and the usefulness of fibroblast growth factor 23 (FGF23) as a proposed inflammation-independent iron marker were tested.MethodsConventional iron markers and FGF23 were measured in children with acute falciparum malaria and after 1, 2, 4, and 6 weeks. Children, who were transfused or received iron supplementation in the follow-up period, were excluded, and iron stores were considered to be stable throughout. Ferritin levels 6 weeks after admission were used as a reference for admission iron status and compared with iron markers at different time points.ResultsThere were long-term perturbations in iron markers during convalescence from acute malaria. None of the tested iron parameters, including FGF23, were independent of inflammation. CRP and AGP normalized faster than ferritin after malaria episodes.ConclusionMalaria may bias epidemiological studies based on inflammation-dependent iron markers. Better markers of iron status during and after inflammation are needed in order to test strategies for iron supplementation in populations at risk of malaria.
Highlights
Most epidemiological studies on the interplay between iron deficiency and malaria risk classify individuals as iron-deficient or iron-replete based on inflammation-dependent iron markers and adjustment for inflammation by using C-reactive protein (CRP) or α-1-acid glycoprotein (AGP)
Study site and participants The study was conducted in Hohoe, a town located about 220 km northeast of Accra, in an area of tropical, semi-deciduous, forest vegetation and used a convenience sample of children included in the MAVARECA study (Malaria Vaccine and Research Capacity Building in Ghana) [21]
During the follow-up period, patients were excluded if they presented with malaria, other severe disease or new spikes in inflammatory markers (C-reactive protein (CRP) > 5 mg/L or α-1-acid glycoprotein (AGP) > 1 g/L), or had taken iron supplementation
Summary
Most epidemiological studies on the interplay between iron deficiency and malaria risk classify individuals as iron-deficient or iron-replete based on inflammation-dependent iron markers and adjustment for inflammation by using C-reactive protein (CRP) or α-1-acid glycoprotein (AGP). The validity of this approach and the usefulness of fibroblast growth factor 23 (FGF23) as a proposed inflammation-independent iron marker were tested. Ferritin is an acute phase protein [15], so in an acute inflammatory situation, such as during malaria, serum ferritin levels may not accurately reflect body iron stores. The intention was to use ferritin levels after normalization post infection as an indication of the true iron status during an acute malaria attack
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